Hyperpolarized 15N-pyridine derivatives as pH-sensitive MRI agents.

Weina Jiang,Shanrong Zhang,Zoltan Kovacs,Wei Chen,Chalermchai Khemtong,A Dean Sherry,Lloyd Lumata

doi:10.1038/srep09104

Abstract

Highly sensitive MR imaging agents that can accurately and rapidly monitor changes in pH would have diagnostic and prognostic value for many diseases. Here, we report an investigation of hyperpolarized 15N-pyridine derivatives as ultrasensitive pH-sensitive imaging probes. These molecules are easily polarized to high levels using standard dynamic nuclear polarization (DNP) techniques and their 15N chemical shifts were found to be highly sensitive to pH. These probes displayed sharp 15N resonances and large differences in chemical shifts (Δδ >90 ppm) between their free base and protonated forms. These favorable features make these agents highly suitable candidates for the detection of small changes in tissue pH near physiological values.

Highlights

Sensitive MR imaging agents that can accurately and rapidly monitor changes in pH would have diagnostic and prognostic value for many diseases
Pyridine derivatives were chosen for evaluation because it is known that their 15N resonances have relatively long T1’s and are highly pH-sensitive[23]
We investigated dynamic nuclear polarization (DNP) hyperpolarization as a means to improve the 15N NMR sensitivity of pH-sensitive pyridine derivatives

Summary

Introduction

Sensitive MR imaging agents that can accurately and rapidly monitor changes in pH would have diagnostic and prognostic value for many diseases. We report an investigation of hyperpolarized 15N-pyridine derivatives as ultrasensitive pH-sensitive imaging probes These molecules are polarized to high levels using standard dynamic nuclear polarization (DNP) techniques and their 15N chemical shifts were found to be highly sensitive to pH. These probes displayed sharp 15N resonances and large differences in chemical shifts (Dd .90 ppm) between their free base and protonated forms. These favorable features make these agents highly suitable candidates for the detection of small changes in tissue pH near physiological values. It has been shown that some 15N-labeled functional groups such as 15N-enriched choline (,4 min)[24], and 15N-enriched nitro compounds (,100 s)[25] have much longer T1 than carbonyl 13C centers

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Conclusion